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MIPOMERSEN

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Mipomersen sodium is an oligonucleotide inhibitor of apolipoprotein B-100 synthesis. It is used as an adjunct to lipid-lowering medications and diet to reduce LDL-C, apolipoprotein B, total cholesterol, and non-HDL-C in adults with homozygous familial hypercholesterolemia.

Specific Substances

    1) Mipomersenum
    2) CAS 1000120-98-8
    1.2.1) MOLECULAR FORMULA
    1) C230-H305-N67-O122-P19-S19-Na19 (Prod Info KYNAMRO(TM) subcutaneous injection, 2013)

Available Forms Sources

    A) FORMS
    1) Mipomersen is available as single-use pre-filled syringes and vials containing 1 mL of a 200 mg/mL solution (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    B) USES
    1) Mipomersen is indicated as an adjunct to lipid-lowering medications and diet to reduce LDL-C, apolipoprotein B, total cholesterol, and non-HDL-C in adults with homozygous familial hypercholesterolemia (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Mipomersen is indicated as an adjunct to lipid-lowering medications and diet to reduce LDL-C, apolipoprotein B, total cholesterol, and non-HDL-C in adults with homozygous familial hypercholesterolemia.
    B) PHARMACOLOGY: Mipomersen sodium is an oligonucleotide inhibitor of apo B-100 synthesis. Apo B is the principal apolipoprotein of LDL and VLDL. Inhibition of translation of the apo B-100 protein results in decreased LDL and VLDL levels.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) COMMON: Injection site reactions, flu-like symptoms, nausea, headache, and elevations of liver enzymes. OTHER EFFECTS: Headache, fatigue, angina, peripheral edema, hypertension, vomiting, abdominal pain, proteinuria, hypersensitivity reaction, pain in extremity, fever, and chills.
    E) WITH POISONING/EXPOSURE
    1) Overdose data are limited. It is anticipated that overdose effects may be an extension of events reported with therapeutic use.
    0.2.20) REPRODUCTIVE
    A) Mipomersen has been classified as pregnancy category B. There are no adequate or well controlled studies of mipomersen use in human pregnancy.
    0.2.21) CARCINOGENICITY
    A) In clinical trials, benign and malignant neoplasms were reported in patients receiving mipomersen.

Laboratory Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs, serum electrolytes, renal function, and liver enzymes after significant overdose.

Treatment Overview

    0.4.6) PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Correct any significant electrolyte abnormalities in patients with severe vomiting.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Severe toxicity is not expected after an overdose.
    C) DECONTAMINATION
    1) PREHOSPITAL: Mipomersen is administered parenterally, GI decontamination is not necessary.
    2) HOSPITAL: Mipomersen is administered parenterally, GI decontamination is not necessary.
    D) AIRWAY MANAGEMENT
    1) Airway management is very unlikely to be necessary unless more toxic agents are involved.
    E) ANTIDOTE
    1) None.
    F) HYPERSENSITIVITY REACTION
    1) MILD/MODERATE: Antihistamines with or without inhaled beta agonists, corticosteroids or epinephrine. SEVERE: Administer oxygen, aggressive airway management, antihistamines, epinephrine, corticosteroids, ECG monitoring, and IV fluids.
    G) ENHANCED ELIMINATION
    1) Hemodialysis is NOT expected to significantly enhance the clearance of mipomersen due to extensive protein binding.
    H) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    2) OBSERVATION CRITERIA: Patients who are symptomatic and patients with deliberate overdose should be observed with frequent monitoring of vital signs. Patients that remain asymptomatic can be discharged.
    3) ADMISSION CRITERIA: Patients who remain symptomatic despite treatment should be admitted.
    4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    I) PITFALLS
    1) When managing a suspected overdose, the possibility of multidrug involvement should be considered. Symptoms of overdose are similar to reported side effects of the medication.
    J) PHARMACOKINETICS
    1) Tmax: SubQ; 3 to 4 hours. Bioavailability: 54% to 78% following SubQ administration of 50 mg to 400 mg mipomersen. Protein binding: greater than or equal to 90%. Metabolism: Tissue endonucleases metabolize mipomersen to shorter oligonucleotides that are subsequent substrates for exonucleases. Excretion: Mipomersen is primarily excreted in urine. Within 24 hours post dose, less than 4% of mipomersen and oligonucleotide metabolites were detected in urine within 24 hours. Elimination half-life: Approximately 1 to 2 months.
    K) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that may cause elevated liver enzymes or hypertension.

Range Of Toxicity

    A) TOXICITY: In clinical trials, adverse effects following mipomersen higher doses (300 mg and 400 mg once weekly for 13 weeks) were similar to adverse effects following therapeutic doses (200 mg subQ once weekly); however, they occurred at a higher rate and greater severity.
    B) THERAPEUTIC DOSES: ADULTS: 200 mg subQ once a week, on the same day each week. CHILDREN: The safety and efficacy of mipomersen have not been established in pediatric patients.

Clinical Effects

Summary Of Exposure

    A) USES: Mipomersen is indicated as an adjunct to lipid-lowering medications and diet to reduce LDL-C, apolipoprotein B, total cholesterol, and non-HDL-C in adults with homozygous familial hypercholesterolemia.
    B) PHARMACOLOGY: Mipomersen sodium is an oligonucleotide inhibitor of apo B-100 synthesis. Apo B is the principal apolipoprotein of LDL and VLDL. Inhibition of translation of the apo B-100 protein results in decreased LDL and VLDL levels.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) COMMON: Injection site reactions, flu-like symptoms, nausea, headache, and elevations of liver enzymes. OTHER EFFECTS: Headache, fatigue, angina, peripheral edema, hypertension, vomiting, abdominal pain, proteinuria, hypersensitivity reaction, pain in extremity, fever, and chills.
    E) WITH POISONING/EXPOSURE
    1) Overdose data are limited. It is anticipated that overdose effects may be an extension of events reported with therapeutic use.

Vital Signs

    3.3.4) BLOOD PRESSURE
    A) WITH THERAPEUTIC USE
    1) FEVER: Fever occurred in 8% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 3% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years) (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) ANGINA
    1) WITH THERAPEUTIC USE
    a) Angina pectoris occurred in 4% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 2% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years) (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    B) PERIPHERAL EDEMA
    1) WITH THERAPEUTIC USE
    a) Peripheral edema occurred in 5% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 2% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years). Subjects 65 years or older who were treated with mipomersen were more likely to develop peripheral edema compared with younger mipomersen-treated subjects (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    C) HYPERTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) Hypertension occurred in 7% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 3% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years). Subjects 65 years or older who were treated with mipomersen were more likely to develop hypertension compared with younger mipomersen-treated subjects (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) WITH THERAPEUTIC USE
    a) Headache occurred in 12% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 9% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years) (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    B) FATIGUE
    1) WITH THERAPEUTIC USE
    a) Fatigue occurred in 15% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 8% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years) (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA
    1) WITH THERAPEUTIC USE
    a) Nausea occurred in 14% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 8% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years) (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    B) VOMITING
    1) WITH THERAPEUTIC USE
    a) Vomiting occurred in 4% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 2% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years) (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    C) ABDOMINAL PAIN
    1) WITH THERAPEUTIC USE
    a) Abdominal pain occurred in 3% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 1% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years) (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) STEATOSIS OF LIVER
    1) WITH THERAPEUTIC USE
    a) Mipomersen is shown to increase hepatic fat (steatosis), which may be accompanied by transaminase increases. In clinical trials, patients experienced a 10% median absolute increase in hepatic fat with 26 weeks of mipomersen therapy (from 0% at baseline). While hepatic steatosis is associated with higher risk of cirrhosis, steatohepatitis, and other advanced liver disease, long-term consequences of mipomersen-associated hepatic steatosis are unknown (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    b) Hepatic steatosis occurred in 7% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 3% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years). The incidence of hepatic steatosis was greater (13.6%) in mipomersen-treated subjects 65 years or older (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    B) INCREASED LIVER ENZYMES
    1) WITH THERAPEUTIC USE
    a) Elevated liver enzymes occurred in 5% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 1% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years) (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    b) Increased AST levels occurred in 6% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 2% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years) (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    c) Increased ALT levels occurred in 10% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 1% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years) (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    d) Increased ALT level of 3 or more times the ULN or 5 or more times the ULN developed in 12% and 9%, respectively, of patients treated with mipomersen for homozygous familial hypercholesterolemia (n=34) compared with 0% of placebo-treated patients (n=17) in clinical studies (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) PROTEINURIA
    1) WITH THERAPEUTIC USE
    a) Proteinuria (1+ or greater by dipstick measurement) occurred in 9% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 3% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years) (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) INJECTION SITE REACTION
    1) WITH THERAPEUTIC USE
    a) Injection site reactions, including erythema, pain, hematoma, pruritus, swelling, discoloration, nodule, rash, warmth, induration, recall reactions, edema, hemorrhage, discomfort, papule, inflammation, macule, vesicles, or urticaria, occurred in 84% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 33% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years). Injection site reactions did not occur with every injection, but led to treatment discontinuation in 5% of subjects in clinical trials (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) PAIN
    1) WITH THERAPEUTIC USE
    a) Musculoskeletal pain occurred in 4% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 2% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years) (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    b) Pain in extremity occurred in 7% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 3% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years) (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ANTIBODY DEVELOPMENT
    1) WITH THERAPEUTIC USE
    a) Mipomersen antibodies developed in 38% of treated subjects in pooled data from 4 clinical trials (n=261). In an open-label extension trial, 72% of mipomersen-treated subjects tested antibody-positive (35% with titers above 3200; n=141). Antibody-positive patients experienced higher trough levels of mipomersen, more flu-like symptoms, and a greater incidence of treatment discontinuation (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    B) HYPERSENSITIVITY REACTION
    1) WITH THERAPEUTIC USE
    a) Hypersensitivity reaction with angioedema occurred in 1 subject treated with mipomersen sodium 200 mg injection in an open-label extension study with a median treatment length of 18.2 months (n=141) (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).

Reproductive

    3.20.1) SUMMARY
    A) Mipomersen has been classified as pregnancy category B. There are no adequate or well controlled studies of mipomersen use in human pregnancy.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) During animal reproduction and embryofetal development studies, administration of subQ mipomersen 87.5 mg/kg/wk (approximately 2 times the clinical exposure of 200 mg/wk) in mice during mating and through organogenesis showed no evidence of fetal harm or impaired fertility. Similarly, subQ mipomersen 52.5 mg/kg/wk (approximately 5 times the clinical exposure of 200 mg/wk) in rabbits did not result in fertility impairment or fetal harm. Lastly, administration of subQ mipomersen 7, 35, and 70 mg/kg/wk in pregnant rats from gestation day 6 through lactation day 20 resulted in decreased pup survival at the highest dose. Decreases in body weight, impaired reflexes, and decreased grip strength were observed at 35 mg/kg/wk and appeared to be dose related (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) There are no adequate or well controlled studies of mipomersen use in human pregnancy (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    B) PREGNANCY CATEGORY
    1) Mipomersen has been classified as pregnancy category B (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    C) ANIMAL STUDIES
    1) During animal reproduction and embryofetal development studies, administration of subQ mipomersen 87.5 mg/kg/wk (approximately 2 times the clinical exposure of 200 mg/wk) in mice during mating and through organogenesis showed no evidence of fetal harm or impaired fertility. Similarly, subQ mipomersen 52.5 mg/kg/wk (approximately 5 times the clinical exposure of 200 mg/wk) in rabbits did not result in fertility impairment or fetal harm. Lastly, administration of subQ mipomersen 7, 35, and 70 mg/kg/wk in pregnant rats from gestation day 6 through lactation day 20 resulted in decreased pup survival at the highest dose. Decreases in body weight, impaired reflexes, and decreased grip strength were observed at 35 mg/kg/wk and appeared to be dose related (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) Lactation studies with mipomersen have not been conducted in humans. Due to the lack of human data and because many drugs are excreted in human milk, the manufacturer recommends discontinuing treatment or discontinuing nursing taking into account the importance of drug to the mother (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    B) ANIMAL STUDIES
    1) Administration of subQ mipomersen up to 70 mg/kg/wk resulted in detectable levels of mipomersin in rat milk (less than or equal to 0.92 mcg/mL). The oral bioavailability of mipomersen is expected to be less than 10% (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) In animal studies, no fertility effects were observed after mice were administered mipomersen sodium doses up to 87.5 mg/kg/wk (2-times the clinical exposure at the 200 mg/wk dose) (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) In clinical trials, benign and malignant neoplasms were reported in patients receiving mipomersen.
    3.21.3) HUMAN STUDIES
    A) NEOPLASM
    1) Benign and malignant neoplasms were reported in 4% of subjects treated with mipomersen sodium 200 mg subQ (n=261) compared with 0% of subjects who received placebo (n=129) in pooled data from 4 clinical studies (age range, 12 to 81 years) (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    3.21.4) ANIMAL STUDIES
    A) ANIMAL STUDIES
    1) Following the administration of subcutaneous mipomersen sodium doses of 5, 20, 60 mg/kg/wk for up to 104 weeks, statistically significant increases in the incidences of hepatocellular adenoma and combined adenoma and carcinoma were observed in female mice after the mipomersen dose of 60 mg/kg/wk (2-times the systemic clinical exposure at 200 mg/wk). Following the same dose of mipomersen, statistically significant increases were found in the incidence of hemangiosarcomas in female mice and fibrosarcomas of the skin/subcutis in male mice (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).
    2) Following the administration of subcutaneous mipomersen sodium doses of 3, 10, 20 mg/kg/wk for up to 104 weeks, statistically significant increases in the incidences of fibrosarcomas of the skin/subcutis and the combination of fibroma, fibrosarcomas and malignant fibrous histiocytoma of the skin/subcutis were observed in female rats after the mipomersen dose of 10 mg/kg/wk (less than the clinical exposure at 200 mg/wk). Following the mipomersen dose of 20 mg/kg/wk (at clinical exposure at the 200 mg/wk), statistically significant increases in the incidence of malignant fibrous histiocytoma of the skin/subcutis were observed in both sexes of rats (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).

Genotoxicity

    A) Mipomersen was not genotoxic in several studies, including the in vitro Bacterial Reverse Mutation (Ames) assay, an in vitro cytogenetics assay using a mouse lymphoma cell line, and an in vivo micronucleus assay in mice (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs, serum electrolytes, renal function, and liver enzymes after significant overdose.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.2) DISPOSITION/PARENTERAL EXPOSURE
    6.3.2.1) ADMISSION CRITERIA/PARENTERAL
    A) Patients who remain symptomatic despite treatment should be admitted.
    6.3.2.2) HOME CRITERIA/PARENTERAL
    A) A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    6.3.2.3) CONSULT CRITERIA/PARENTERAL
    A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.2.5) OBSERVATION CRITERIA/PARENTERAL
    A) Patients who are symptomatic and patients with deliberate overdose should be observed with frequent monitoring of vital signs. Patients that remain asymptomatic can be discharged.

Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs, serum electrolytes, renal function, and liver enzymes after significant overdose.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Mipomersen is administered parenterally, GI decontamination is not necessary.
    6.5.3) TREATMENT
    A) SUPPORT
    1) Treatment should include recommendations listed in the PARENTERAL EXPOSURE section when appropriate.

Enhanced Elimination

    A) HEMODIALYSIS
    1) Hemodialysis is NOT expected to significantly enhance the clearance of mipomersen due to extensive protein binding.

Range Of Toxicity

Summary

    A) TOXICITY: In clinical trials, adverse effects following mipomersen higher doses (300 mg and 400 mg once weekly for 13 weeks) were similar to adverse effects following therapeutic doses (200 mg subQ once weekly); however, they occurred at a higher rate and greater severity.
    B) THERAPEUTIC DOSES: ADULTS: 200 mg subQ once a week, on the same day each week. CHILDREN: The safety and efficacy of mipomersen have not been established in pediatric patients.

Therapeutic Dose

    7.2.1) ADULT
    A) 200 mg SubQ once a week, on the same day each week (Prod Info KYNAMRO(TM) subcutaneous injection, 2013)
    7.2.2) PEDIATRIC
    A) The safety and efficacy of mipomersen have not been established in pediatric patients (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).

Maximum Tolerated Exposure

    A) In clinical trials, adverse effects following mipomersen higher doses (300 mg and 400 mg subQ once weekly for 13 weeks) were similar to adverse effects following therapeutic doses (200 mg subQ once weekly); however, they occurred at a higher rate and greater severity (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Mipomersen sodium is an oligonucleotide inhibitor of apo B-100 synthesis, inhibiting synthesis of apo B by sequence-specific binding to its messenger ribonucleic acid (mRNA) through enzyme-mediated pathways or disruption of mRNA function through binding alone. Apo B is the principal apolipoprotein of LDL and VLDL. Its binding to apo B mRNA as a complement in the coding region of the apo B-100 mRNA, allows hybridization of mipomersen to the cognate mRNA and RNase H-mediated degradation of the cognate mRNA with inhibition of translation of the apo B-100 protein resulting in decreased LDL and VLDL levels (Prod Info KYNAMRO(TM) subcutaneous injection, 2013).

Physicochemical

Molecular Weight

    A) 7594.9 g/mol (Prod Info KYNAMRO(TM) subcutaneous injection, 2013)

References

General Bibliography

    1) Lieberman P, Nicklas R, Randolph C, et al: Anaphylaxis-a practice parameter update 2015. Ann Allergy Asthma Immunol 2015; 115(5):341-384.
    2) Lieberman P, Nicklas RA, Oppenheimer J, et al: The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol 2010; 126(3):477-480.
    3) National Heart,Lung,and Blood Institute: Expert panel report 3: guidelines for the diagnosis and management of asthma. National Heart,Lung,and Blood Institute. Bethesda, MD. 2007. Available from URL: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
    4) Nowak RM & Macias CG : Anaphylaxis on the other front line: perspectives from the emergency department. Am J Med 2014; 127(1 Suppl):S34-S44.
    5) Product Information: KYNAMRO(TM) subcutaneous injection, mipomersen sodium subcutaneous injection. Genzyme Corporation (per manufacturer), Cambridge, MA, 2013.
    6) Product Information: diphenhydramine HCl intravenous injection solution, intramuscular injection solution, diphenhydramine HCl intravenous injection solution, intramuscular injection solution. Hospira, Inc. (per DailyMed), Lake Forest, IL, 2013.
    7) Vanden Hoek,TL; Morrison LJ; Shuster M; et al: Part 12: Cardiac Arrest in Special Situations 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. American Heart Association. Dallas, TX. 2010. Available from URL: http://circ.ahajournals.org/cgi/reprint/122/18_suppl_3/S829. As accessed 2010-10-21.